Work has been continued to obtain information relative to the inter-relationship between primary tumor and the tumor specific immune response of the host. It has the ultimate aim of developing therapeutic strategies against micrometastases and of determining how the presence or absence of a primary tumor is involved. Evidence was obtained for the first time demonstrating that macrophages from colonies produced by colony forming cells (CFC) of bone marrow were cytotoxic to cells from an immunizing tumor and continued to possess cytotoxicity for as long as the tumor was present. By 21 days following tumor removal cytotoxicity of the cells was lost. The findings suggest that the cytotoxicity of the macrophage originates in the concentral CFCs. Other investigators correlated the effect of chemo-immunotherapy with bone marrow macrophage precursor cell stimulation and macrophage cytotoxicity. Findings revealed that although the proportion of cytotoxic macrophages was not altered by C. parvum (CP) when administered with cytoxan (CY) the absolute number of such cells was increased. Additional investigations evaluated (a) the effect of other chemotherapeutic agents than Cy with CP on tumor growth and found that the effect was different depending upon the chemotherapeutic agent employed and (b) the effect of CP on CY metabolism. During the coming year investigations will continue to (1) correlate macrophage or lymphocyte cytotoxicity and serum blocking factor following primary tumor removal with the presence or absence of micrometastases, (2) determine the influence of the presence or absence of a primary tumor on the congregation of immunocytes (lymphocytes or macrophages) at the site of micrometastases and (3) determine the effect of the presence or absence of a primary tumor on the effectiveness of chemotherapy of metastases. BIBLIOGRAPHIC REFERENCES: Further Observations on the Inhibition of Tumor Growth by C. Parvum with Cyclophosphamide: I. Variation in Administration of Both Agents, Fisher, B.; Wolmark, N.; Rubin, H.; Saffer, E. J. Natl Cancer Inst. 55: 1147-53, 1975. Further Observations on the Inhibition of Tumor Growth by C. Parvum with Cyclophosphamide: II. Effect of Cortisone Acetate. Fisher, B.; Rubin, H.; Saffer, E.; Wolmark, N. J. Natl Cancer Inst. 56:571-74, 1976.